title: Erythropoietin administration modulates pulmonary Nrf2 signaling pathway after traumatic brain injury in mice.
abstract: BACKGROUND
  In our previous studies, antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has been shown to play an important role in protecting traumatic brain injury (TBI)-induced acute lung injury (ALI). This study was designed to explore whether recombinant human erythropoietin (rhEPO) administration modulates pulmonary Nrf2 signaling pathway in a murine TBI model.
  
  
  METHODS
  Closed head injury was made by Hall's weight-dropping method. The rhEPO was administered at a dose of 5,000 IU/kg 30 minutes after TBI. Pulmonary capillary permeability, wet or dry weight ratio, apoptosis, Nrf2 and its downstream cytoprotective enzymes including NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase were investigated at 24 hours after TBI.
  
  
  RESULTS
  We found that treatment with rhEPO markedly ameliorated TBI-induced ALI, as characterized by decreased pulmonary capillary permeability, wet or dry weight ratio, and alveolar cells apoptosis. Administration of rhEPO also significantly upregulated the mRNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase.
  
  
  CONCLUSIONS
  The results of this study suggest that post-TBI rhEPO administration may induce Nrf2-mediated cytoprotective response in the lung, and this may be a mechanism whereby rhEPO reduces TBI-induced ALI.
authors.affiliation: Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Kong
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ni
authors.forename: Weibang
authors.initials: W
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D002199:Capillary Permeability / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051267:NF-E2-Related Factor 2; D004921:Erythropoietin